Abstract This new program is a marriage of three important research fields; Drug Addiction, Sex Differences, and Environmental Health. Sex differences in drug-related behaviors have been well documented and attributed to actions of estrogens and progesterone in adult females. Here we move beyond this hypothesis and examine two other factors both of which have been implicated in reward via their actions on the dopamine system. Endocrine disruptors (EDCs) are ubiquitous in the environment and are known to alter sex differences in brain and behavior. EDC exposure is particularly potent when it occurs during neonatal development. As such it is a model for fetal origins of adult disease. This two-year grant will test the hypothesis that exposure to Bisphenol A (BPA), one of the well-studied and abundant EDCs in the environment, can increase vulnerability to cocaine. To further dissect the role of gender on drug vulnerability the four core genotype (FCG) mouse model will be used. The FCG allows separate analysis of gonadal hormones and sex chromosome complement (XX vs. XY). In aim one a dose-response study will be conducted with BPA exposure during gestation. In the next aim the FCG mice will be tested. Adult mice are fitted with chronic indwelling jugular cannula which allow them to self-administer cocaine. Fixed and progressive ratio schedules are used to examine self-administration and measure both acquisition and maintenance. The long term objectives of this work are to develop a research program to test the effects of environmental endocrine disrupting compounds in combination with gender, on motivated drug seeking and taking behavior.